Introduction 

How does muscle weakness associated with Kearns-Sayre Syndrome affect one’s mobility and functionality over time?

defects in the mitochondria, which are essential for producing energy for the body. KSS can result in a wide range of symptoms in the body.

Kearns-Sayre Syndrome (KSS) is a rare neuromuscular condition caused by mutations in mitochondrial DNA. Mitochondria are organelles (organs of cells) found in all cells except red blood cells. These play an important role in producing energy for the body; hence, damage to these structures impairs their function. As these organelles are found throughout the body, patients with KSS present with muscle weakness in various parts of the body. Basic movements, such as walking and standing, and fine movements, including control of the eye, can be profoundly affected. Individuals with KSS, therefore, face a multitude of challenges in their daily life, which affects their well-being. This article seeks to explore the causes, effects and supportive management of muscle weakness in KSS, to spread awareness and help improve the quality of life for those affected and their loved ones. 

Understanding muscle weakness in KSS 

Causes 

Mitochondrial dysfunction 

In Kearns-Sayre Syndrome (KSS), muscle weakness primarily occurs due to problems with the mitochondria, the tiny powerhouse within our cells for energy production. While there are genetic mutations and deletions in mitochondrial DNA (mtDNA), the ability to effectively generate energy is disrupted. 

The energy production process involved (oxidative phosphorylation) is impaired, resulting in a shortage of energy (ATP) supply to the muscles. Hence, diminishes the muscles’ ability to contract and relax properly, leading to weakness, reduced endurance, and fatigue. 

As muscles require significant amounts of energy, a shortage of energy can often result in generalised muscle weakness throughout the body, leading to difficulty in sustaining movements or engaging in physical activities for long periods.¹

Muscle fibre damage

Weakness in KSS is also linked to damage to muscle fibres.  Defective mitochondria often accumulate in skeletal and ocular muscles, demonstrated as ragged red muscle fibres when stained, similar to other mitochondrial myopathies. Severe demyelination of the brain’s white matter tracts is also found in some instances, likely indicating further muscle weakness due to debilitated neuronal control.¹

Who does it affect?

Despite being rare, KSS are estimated to affect 1 to 3 people out of every 100,000, with an onset before age 20, and symptoms progressively worsen over time.²

Characteristics of muscle weakness 

Chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (PEO) is characterised by gradual weakness or paralysis of extraocular muscles that leads to bilateral droopy eyelids (ptosis) and limited eye movements. This has been a hallmark of KSS due to the exceptionally high mitochondrial energy production among the eye muscles, which require sustained activity. It often begins in adolescence, causing individuals to turn their heads to see in different directions. Some may even lose the ability, resulting in a fixed gaze over time.³ 

Facial and limb weakness

A myopathic presentation of facial and limb weakness can develop gradually with varying severity in KSS. Facial weakness often manifests as a mask-like appearance, characterised by reduced facial expressions and eyelid closure or opening. Individuals may also experience difficulty swallowing (dysphagia) occasionally when muscles for mastication (chewing) are involved. As the disease progresses, weakness can become diffused, spreading to the neck, shoulder muscles, and even causing weakness in the extremities of the limbs.^1,3

Proximal muscle involvement

Proximal muscle weakness is prominent upon KSS, typically affecting muscles closest to the trunk, such as the neck, shoulders, arms, legs, and hips. Patients may experience difficulty with activities requiring proximal strength and endurance, such as rising from a seated position, climbing stairs, or lifting objects overhead. Proximal weakness is slowly progressive, contributing to fatigue and reduced mobility over time.  Distal muscles are generally less affected, reflecting mitochondrial energy production and impairment in high-metabolism-demanding muscles, consistent with the systematic nature of KSS as a mitochondrial disorder.^1,3

Functional limitations 

Ocular and visual limitations 

PEO, as a hallmark of KSS, can significantly hinder eye movement, making tasks such as reading, tracking moving objects, or scanning environments exceptionally difficult. Nonetheless, drooping eyelids can further obstruct visual fields, requiring compensatory head postures or surgical corrections. These limitations significantly impact communication, learning, and daily interactions in visually demanding settings.  

Facial, speech and swallowing difficulties 

Facial muscle weakness can reduce facial expression, affecting verbal communication. Weakness in the oropharyngeal muscles can lead to difficulty articulating words clearly and slurred speech (dysarthria). Swallowing difficulty can also develop at later stages, leading to challenges with eating and an increased risk of choking and aspiration, which impacts nutrition and respiratory health.^1,3

Upper limb and fine motor impairments 

KSS can lead to mild to moderate weakness in the arms and hands, making tasks like lifting objects, dressing, grooming, feeding, or handling small items more challenging. Additionally, fine motor tasks, like writing or typing, can also be hindered, limiting productivity and independence in academic or work settings. 

Generalised fatigue and exercise intolerance 

Alongside muscle weakness, individuals with KSS often experience profound fatigue affecting participation in a wide range of activities. It is often disproportionate to the level of exertion and does not resolve quickly with rest. This persistent fatigue limits executive functioning, social activities, schooling and work engagement, as well as the completion of daily routines without frequent breaks.³

Impact on mobility 

Reduced endurance and fatigue

Reduced endurance can vastly impact mobility in those with KSS. As mitochondrial function is impaired, muscles are unable to sustain prolonged activity, resulting in rapid, disproportionate fatigue even during routine tasks like walking or climbing stairs. Unlike sudden paralysis, the fatigue is gradual and worsens with exertion. The decreased stamina could limit physical independence, necessitating frequent rest breaks or use of assistive devices, like a cane, walker, or wheelchair, over time for energy conservation and independence.  

Balance, coordination and gait disturbances 

Balance and coordination issues are significant contributors to mobility impairment in KSS. It arises from leg and core muscle weakness, combined with proprioception and occasional cerebellar involvement (ataxia).⁴ Individuals may experience difficulty with postural or stability maintenance when standing or walking. Additionally, they may develop a slow, shuffling, unsteady gait with widened stance to maintain balance, especially on uneven surfaces or during directional changes. As proximal muscles weaken, leg lifting can become increasingly difficult, causing constant leg dragging or frequent tripping. As fatigue further diminishes gait quality over time, the effort and energy required for movements also increases.

Postural instability and increased fall risk

Weakness in core muscles can affect the ability to maintain an upright posture. Movements such as rising from a chair, changing directions, or maintaining balance on stairs become difficult. With the mutual effects of muscle weakness and coordination impairments, the risk of falls increases. Individuals may become more susceptible to tripping, stumbling, or losing their balance during postural shifts or sudden movements. Over time, this leads to a high risk of injury, reduced confidence, fear of movement, and worsened mobility restriction.  

Musculoskeletal complications 

Musculoskeletal complications can often arise in KSS as a result of chronic muscle weakness and imbalance. Scoliosis and foot drop are common due to weakened spinal muscles and impaired lower leg muscle control, respectively.^5,6 They can alter posture and gait in the long run, which can increase discomfort and the risk of falls. Joint contractures may also develop over time as movements are reduced, further limiting the range of motion and functional independence. 

Management and support 

Physical and occupational therapy

Physical and occupational therapy can be supportive of the KSS management. Physical therapy focuses on preserving muscle strength, improving endurance, and enhancing postural stability through low-intensity exercise and stretching.⁷ Occupational therapy can facilitate adaptation to daily activities and promote self-care and communication independence.⁸ While rehabilitation therapies are unable to alter or reverse disease progression, they can significantly promote functional ability, safety in daily routines, and prevent complications. 

Mobility aids and assistive devices 

Mobility aids are often crucial in facilitating KSS individuals' ability to get around as muscle weakness and fatigue progress. Canes, walkers, and rollators can support balance and reduce the risk of falls in the early stages. As muscle strength and endurance decline, wheelchairs, either lightweight or power-assisted models, may be necessary to conserve energy and support independence for long-distance travel. Custom orthotics or braces may also be used when necessary to address gait abnormalities or ankle instability. 

While the selection of mobility aids is personally advised by physiotherapists or occupational therapists, taking into consideration individuals’ strength, stamina, and daily needs, regular reassessments are also necessary to adapt to functional abilities over time.

Energy conservation strategies

Energy conservation strategies are vital for the KSS population in managing fatigue and maintaining daily function^7,8,9. Pacing activities by alternating periods with rest, prioritising essential tasks, and planning the day can avoid unnecessary energy depletion. The use of adaptive tools and simplifying movement during essential tasks can also reduce physical strains. Furthermore, environmental modifications like arranging items within easy reach can also help minimise effort, promoting independence and reducing overexertion. 

Multidisciplinary care

Multidisciplinary care is essential in managing KSS muscle weakness due to its complex, multisystem involvement. While neurologists and geneticists can closely monitor disease progression and coordinate care, physical and occupational therapists help address mobility, endurance, and daily function. Speech and language therapists manage communication and swallowing issues, and cardiologists oversee cardiac conduction abnormalities. Dietitians can also help support nutritional needs by compensating for swallowing impairments. 

Summary 

Muscle weakness in Kearns-Sayre Syndrome can significantly reduce an individual’s mobility and functional independence. Its complexity and multisystem involvement have highlighted the importance of early intervention, timely therapy and supportive care. When provided by empathetic multidisciplinary care teams that involve neurological and genetic specialists, as well as rehabilitation therapists, mobility and functionality can still be preserved to the greatest extent, improving the quality of life for those affected by this rare condition.